Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.23 (MMP)
 4,246 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The function of many transmembrane molecules can be altered by cleavage and subsequent release of their ectodomains. We have investigated ectodomain cleavage of the cell-cell adhesion and signal-transducing molecule E-cadherin. The E-cadherin ectodomain is constitutively shed from the surface of MCF-7 and MDCKts.srcC12 cells in culture. Release of the 80 kDa soluble E-cadherin fragment is stimulated by phorbol-12-myristate-13-acetate and is inhibited by overexpression of the tissue inhibitor of metalloproteinases-2. The metalloproteinases matrilysin and stromelysin-1 both cleave E-cadherin at the cell surface and release sE-CAD into the medium. The soluble E-cadherin fragment thus released inhibits E-cadherin functions in a paracrine way, as indicated by induction of invasion into collagen type I and inhibition of E-cadherin-dependent cell aggregation. Our results, therefore, suggest a novel mechanism by which metalloproteinases can influence invasion.
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PMID:Release of an invasion promoter E-cadherin fragment by matrilysin and stromelysin-1. 1111 95

Circulating and vascular endothelin-1 (ET-1) levels are elevated in diabetes, but the molecular components of the enzymatic activation of ET-1 in the vasculature remains unknown. Furthermore, the distribution of ET receptors favors a contractile phenotype in African Americans with diabetes. Whether there is any difference in local ET-1 activation in this population is unknown. This study examined the expression and activity of ET converting enzyme-1 subisoforms (ECE-1) in the internal mammary artery specimens obtained from patients undergoing coronary artery bypass grafting. The study groups included African-American (AA) and Caucasian (CA), nondiabetic (ND) and diabetic (D) patients: AAND N = 10, CAND N = 9, AAD N = 9, and CAD N = 11. The expression of ECE-1 a, ECE-1 b and ECE-1c subisoforms was studied by RT-PCR. ECE-1 a was upregulated 2- and 4-fold in the CAD and MD groups, respectively (P < .05). In African-American patient groups, ECE-1 activity (fmol/ mg protein.h) was augmented from 2,804 +/- 185 in nondiabetic tissue samples to 6,857 +/- 393 in the diabetic tissue (P < .05). There was a similar increase in the CAD group, which did not significantly differ from AA diabetics. ECE-1 inhibitors, phosphoramidon and FR-901533, inhibited vascular ECE-1 activity by more than 80%. While neutral endopeptidase (NEP) and matrix metalloproteinase-2 (MMP-2) are able to process big ET-1, inhibitors of NEP (thiorphan) and MMP (batimistat) did not affect ECE-1 activity. In conclusion, the enzymatic pathway essential for generating vascular ET-1 is activated in the vasculature of both AA and CA diabetic patients and this activation is highly specific for ECE-1.
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PMID:Vascular endothelin converting enzyme-1 expression and activity is upregulated in clinical diabetes. 1247 47

Excessive wound exudates are troublesome symptoms of malignant fungating wounds. In particular, such exudates may cause periwound moisture-associated dermatitis (MAD). In this study, we focused on factors that contribute to skin irritation by exudates in breast cancer patients with malignant fungating wounds. Our aim was to identify the relationship between MAD surrounding malignant fungating wounds and levels of various candidate irritating factors in their exudates. We recruited 20 breast cancer patients with exudates from malignant fungating wounds and collected three types of exudate samples: pooled exudate, swab, and fresh exudate samples. We measured the pH, concentrations of polyamines (putrescine [PUT], cadaverine [CAD], spermidine, and spermine), and matrix metalloproteinases (MMP2 and MMP9) in the exudates and cultured them for bacteria. Differences between participants with and without MAD were assessed using Fisher's exact test or the Mann-Whitney U test. Of the 20 participants, 14 had MAD. There were no significant differences in median pH and MMP activity between patients with and without MAD. The level of PUT was significantly higher in the MAD than in the non-MAD group (p = .008), and CAD was detected only in the MAD group (p = .016). Prospective studies are needed to clarify correlations and causal relationships between polyamines and erythema and identify therapeutic targets for preventing the development of MAD.
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PMID:Association Between Components of Exudates and Periwound Moisture-Associated Dermatitis in Breast Cancer Patients With Malignant Fungating Wounds. 2618 Jan 82